The present invention relates to a method of preparing a freeze-dried powder, which can be used to quickly and conveniently generate a liposomal formulation of a polyene such as nystatin.
Nystatin is a tetraene-diene polyene antibiotic, first isolated from Streptomyces noursei, which is used in the treatment of various fungal infections. Unfortunately, nystatin, as well as other polyenes, is not generally useful for parenteral administration, because of its high toxicity and insolubility in water. A formulation of a polyene, such as nystatin, which could be administered parenterally would substantially enhance the drug's therapeutic usefulness.
Some of the inventors of this patent previously discovered that these problems could be overcome by formulating nystatin in phospholipid vesicles, or liposomes. Such a liposomal formulation is considerably less toxic to the animal to which it is administered, but is still effective against fungal infection, and therefore is suitable for systemic use. U.S. Pat. No. 4,812,312 discloses that invention, and is incorporated here by reference.
One drawback to some liposomal drug formulations is their less-than-desirable shelf life. Another drawback is the relative complexity of the process needed to prepare them. In view of these drawbacks, it would be highly desirable to produce a stable, dry formulation which could be rehydrated when needed for treatment of a patient. Lyophilized, or freeze-dried, powders are a possible answer to this need. However, in order to be practical, a lyophilized powder must not only be stable and capable of reconstituting as liposomes, it must capable of being prepared by a process that is simple and inexpensive enough so that it will be practical and cost-effective for commercial use.
The present invention solves these and other problems found in the prior art.